Our recent research objective has been to investigate metabolism and its control in normal and injured (wounds, burns, carcinogenesis, and ultraviolet light irradiation) skin. Pedicle flaps have been utilized successfully to reconstruct defects of congenital, traumatic and malignant origins. Free flaps may offer a more versatile means for achieving this goal. The aim of this proposal is to study and compare the metabolic alterations occurring in association with construction and utilization of cutaneous pedicle flaps and free flaps. The surgical procedure of "delaying" pedicle flaps before transfer to a new position improves flap survival. The vascular changes secondary to "dalay" have been well documented and suggest a tissue adaptation to "nonlethal ischemia". We propose the mechanism of "delay" to be a metabolic adaptation of flap tissue to the altered environment. The hypothesized adaptation is one which we have found commonly in healing systems previously studied (wound, UVL irradiation, carcinogenesis). This adaptation is characterized by increased activities of glycolysis and the pentose phosphate shunt. Preliminary data suggest that this adaptive mechanism is responsible for the improved survival of "delayed" flap tissue. This proposal includes the study of intermediate steps of energy metabolism, i.e., assays of enzyme activities and the concentrations of substrates and coenzymes, and the study of overall rates of carbohydrate, amino acid, and nucleic acid metabolism in "undelayed" and "delayed" skin flaps and free flaps. The microanalytical techniques essential to the metabolic investigation of various skin structures such as the epidermis, dermis, subcutaneous muscle, and blood vessels are: (1) fluorometric assay of enzyme octivities; (2) the enzymatic cycling method for measurement of metabolic intermediates and cofactors; (3) microadaptation of radioisotope methods for overall metabolic studies and cyclic AMP metabolism; and (4) microvolumetric measurement of tissue respiration. The difference in biochemical alterations between "undelayed" and "delayed" tissues will provide fundamental information regarding the mechanism of the "delay" phenomenon and its control.